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[慢性肾脏病中的脂质代谢异常]

[Lipid metabolism abnormalities in Chronic Kidney Disease].

作者信息

Bianchi Stefano, Baronti Alessandro, Cominotto Renato, Bigazzi Roberto

出版信息

G Ital Nefrol. 2016;33(S68).

Abstract

Regardless of the etiology of renal disease, patients with chronic kidney disease (CKD) develop profound qualitative and quantitative lipoprotein metabolism abnormalities because of the presence of alterations in apolipoproteins, lipid transfer proteins, lipolytic enzymes, and lipoprotein receptors from the earlier stages of the disease. As renal function deteriorates, triglyceride concentrations increase and high-density lipoprotein cholesterol (HDL) concentrations decline, while levels of low- density lipoprotein (LDL) cholesterol remain in the normal range or become slightly decreased. Meanwhile, there is a progressive accumulation of the more atherogenic small dense LDL particles. In stages 4 and 5 of CKD, there is decreased concentration of apolipoprotein A-containing lipoproteins, and increased concentrations of triglyceride-rich apolipoprotein B-containing lipoproteins. Patients with nephrotic syndrome and preserved glomerular filtration rate show a higher atherogenic profile, with markedly elevated plasma cholesterol, triglyceride concentrations, and increased very low (VLDL) and low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and lipoprotein(a) levels. Depressed plasma HDL cholesterol concentrations are also commonly observed in patients with nephrotic syndrome. Unless nephrotic syndrome is present, lipid abnormalities are not commonly observed when the lipid profile is measured using standard quantitative methods. In particular, total and LDL cholesterol, the most common lipid parameters used to stratify the cardiovascular risk and assess the effect of treatment with statins, are usually normal and often low. However, there is evidence that some alterations of the qualitative profile of lipoprotein are characteristic of chronic kidney disease, and probably contribute to the high rate of atherosclerotic events observed in these patients. These qualitative abnormalities include increased levels of VLDL and IDL cholesterol, small dense and oxidized LDL particles and lipoprotein(a). Moreover, HDL cholesterol is usually low and dysfunctional, not acting as protective, but paradoxically as proatherogenic particles. The lipid profile of CKD shows similar features to the metabolic syndrome and type 2 diabetes, conditions well known to predispose to kidney disease, which in turn aggravates insulin resistance and promotes atherogenic dyslipidemia.

摘要

无论肾病的病因如何,慢性肾脏病(CKD)患者都会出现严重的定性和定量脂蛋白代谢异常,这是因为从疾病早期阶段起,载脂蛋白、脂质转运蛋白、脂解酶和脂蛋白受体就发生了改变。随着肾功能恶化,甘油三酯浓度升高,高密度脂蛋白胆固醇(HDL)浓度下降,而低密度脂蛋白(LDL)胆固醇水平保持在正常范围或略有下降。与此同时,更具动脉粥样硬化性的小而密LDL颗粒逐渐积累。在CKD的4期和5期,含载脂蛋白A的脂蛋白浓度降低,富含甘油三酯的含载脂蛋白B的脂蛋白浓度升高。肾病综合征且肾小球滤过率保留的患者具有更高的动脉粥样硬化风险,其血浆胆固醇、甘油三酯浓度显著升高,极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)、中间密度脂蛋白(IDL)和脂蛋白(a)水平增加。肾病综合征患者通常也会出现血浆HDL胆固醇浓度降低的情况。除非存在肾病综合征,使用标准定量方法测量血脂谱时,通常不会观察到脂质异常。特别是,用于分层心血管风险和评估他汀类药物治疗效果的最常见脂质参数——总胆固醇和LDL胆固醇,通常正常且往往偏低。然而,有证据表明,脂蛋白定性谱的某些改变是慢性肾脏病的特征,可能导致这些患者中观察到的高动脉粥样硬化事件发生率。这些定性异常包括VLDL和IDL胆固醇水平升高、小而密和氧化的LDL颗粒以及脂蛋白(a)。此外,HDL胆固醇通常较低且功能失调,不是起到保护作用,而是反常地起到促动脉粥样硬化颗粒的作用。CKD的血脂谱显示出与代谢综合征和2型糖尿病相似的特征,这两种情况是众所周知的易患肾病的因素,而肾病反过来又会加重胰岛素抵抗并促进动脉粥样硬化性血脂异常。

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